Browsing by Author "Vasquez, Karen M."

Now showing 1 - 4 of 4

Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer
(Frontiers Media S.A., 2021-03-23T00:00:00) Khandelwal, Akanksha; Sharma, Uttam; Barwal, Tushar Singh; Seam, Rajeev Kumar; Gupta, Manish; Rana, Manjit Kaur; Vasquez, Karen M.; Jain, Aklank
Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients. � Copyright � 2021 Khandelwal, Sharma, Barwal, Seam, Gupta, Rana, Vasquez and Jain.
The emerging role of long non-coding RNA in gallbladder cancer pathogenesis
(Elsevier B.V., 2017) Khandelwal, Akanksha; Malhotra, Akshay; Jain, Manju; Vasquez, Karen M.; Jain, Aklank; Khandelwal, A.; Malhotra, A.; Jain, M.; Vasquez, K.M.; Jain, A.
Gallbladder cancer (GBC) is the most common and aggressive form of biliary tract carcinoma with an alarmingly low 5-year survival rate. Despite its high mortality rate, the underlying mechanisms of GBC pathogenesis are not completely understood. Recently, from a growing volume of literature, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression and appear to play vital roles in many human cancers. To date, a number of lncRNAs have been implicated in GBC, but their potential roles in GBC have not been systematically examined. Thus, in this review, we critically discuss the emerging roles of lncRNAs in GBC, and the pathways involved. Specifically, we note that some lncRNAs show greater expression in T1 and T2 tumor stages compared to T3 and T4 tumor stages and that their dysregulation leads to alterations in cell cycle progression and can cause an increase in GBC cell proliferation or apoptosis. In addition, some lncRNAs control the epithelial-mesenchymal transition process, while others take part in the regulation of ERK/MAPK and Ras cancer-associated signaling pathways. We also present their potential utility in diagnosis, prognosis, and/or treatment of GBC. The overall goal of this review is to stimulate interest in the role of lncRNAs in GBC, which may open new avenues in the determination of GBC pathogenesis and may lead to the development of new preventive and therapeutic strategies for GBC. ? 2016 Elsevier B.V. and Soci?t? Fran?aise de Biochimie et Biologie Mol?culaire (SFBBM)
LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3
(Elsevier B.V., 2021-01-11T00:00:00) Sharma, Uttam; Barwal, Tushar Singh; Khandelwal, Akanksha; Malhotra, Akshay; Rana, Manjit Kaur; Singh Rana, Amrit Pal; Imyanitov, Evgeny N.; Vasquez, Karen M.; Jain, Aklank
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with fewer treatment options than other types of invasive breast cancer due to the loss of the estrogen, progesterone receptors and low levels of the HER2 protein, resulting in a poor prognosis for these patients. Here, we found that the expression of the lncRNA, ZFAS1, was significantly downregulated (?3.0-fold) in blood samples of TNBC patients (n=40) compared to matched healthy controls (n=40). Functionally, silencing of ZFAS1 promoted cell proliferation and colonization of human MDA-MB-231 TNBC cells by inhibiting the expression levels of the cyclin-dependent kinase (CDK) inhibitors p21 (CDKN1A) and p27 (CDKN1B) compared to the scrambled siRNA control cells. Further, we found that downregulation of ZFAS1 led to decreased protein levels of the epithelial markers, E-cadherin, Claudin-1, and Zo-1, with increased protein levels of the mesenchymal markers, Slug and ZEB1. In addition, by utilizing the bioinformatic tools such as RAID v2.0 (RNA Interactome Database Version 2.0), AnnoLnc (Annotate human lncRNA database), and GEPIA (Gene Expression Profiling Interactive Analysis), we identified a strong negative correlation between ZFAS1 and signal transducer and activator of transcription 3 (STAT3) gene expression (R = ?0.11, p-value = 0.0002). Further, we observed that decreased ZFAS1 expression significantly (p < 0.05) increased STAT3 and phosphorylated STAT3 (at Ser727 residue) protein levels in TNBC cells. The composite data indicate that ZFAS1 may function as a tumor-suppressor lncRNA with potential as a diagnostic/prognostic marker and may offer a new target for the treatment of TNBC patients. � 2021 Elsevier B.V. and Soci�t� Fran�aise de Biochimie et Biologie Mol�culaire (SFBBM)
The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer
(Impact Journals LLC, 2017) Malhotra, Akshay; Jain, Manju; Prakash, Hridayesh; Vasquez, Karen M.; Jain, Aklank; Malhotra, A.; Jain, M.; Prakash, H.; Vasquez, K.M.; Jain, A.
Chemoresistance is one of the major hurdles in the treatment of breast cancer, which limits the effect of both targeted and conventional therapies in clinical settings. Therefore, understanding the mechanisms underpinning resistance is paramount for developing strategies to circumvent resistance in breast cancer patients. Several published reports have indicated that lncRNAs play a dynamic role in the regulation of both intrinsic and acquired chemoresistance through a variety of mechanisms that endow cells with a drug-resistant phenotype. Although a number of lncRNAs have been implicated in chemoresistance of breast cancer, their mechanistic roles have not been systematically reviewed. Thus, here we present a detailed review on the latest research findings and discoveries on the mechanisms of acquisition of chemoresistance in breast cancer related to lncRNAs, and how lncRNAs take part in various cancer signalling pathways involved in breast cancer cells. Knowledge obtained from this review could assist in the development of new strategies to avoid or reverse drug resistance in breast cancer chemotherapy. ? 2017 Malhotra et al.